HB0025-C-0301: A Study to Investigate HB0025 Combined With Chemotherapy as First-Line Treatment for Advanced or Recurrent MMR-proficient Endometrial Cancer

This is a multicenter, randomized, double-blind, placebo controlled Phase III clinical trial, aiming to evaluate the efficacy and safety of HB0025 combined with chemotherapy (paclitaxel plus carboplatin) versus placebo combined with chemotherapy (paclitaxel plus carboplatin) as a first-line treatment for advanced (Stage III/IV) or recurrent proficient Mismatch Repair Endometrial Cancer（pMMR EC). The trial will take progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) as the primary endpoint, and plans to enroll approximately 333 participants. After being eligible for screening, participants will be randomly assigned to the study arms at a ratio of 2:1 to receive either HB0025 combined with chemotherapy (experimental group) or placebo combined with chemotherapy (control group). Both regimens will be administered once every 3 weeks (Q3W). After completing 6 cycles of combination treatment, patients will enter the maintenance therapy phase with HB0025 or placebo (Q3W) only. The treatment will last until intolerable toxicity occurs, disease progression, lost to follow up or death, withdrawal of consent, pre-scheduled study treatment are completed, receiving new anticancer therapy or sponsor discontinue the study, whichever comes first.

Inclusion Criteria: 1. Female patients aged 18 years or older at screening. 2. Able to fully understand and voluntarily sign the informed consent form, and are willing and able to follow the clinical trial and subsequent visit procedures. 3. Patients diagnosed with advanced (stage III/IV, classified according to the 2009 International Federation of Gynecology and Obstetrics (FIGO)) or recurrent endometrial cancer, whose pathological type include but are not limited to endometrial adenocarcinoma, serous carcinoma, clear cell carcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, mixed carcinoma, carcinosarcoma (excluding uterine sarcoma), and confirmed as pMMR in the central laboratory. 4. Patients who had not received any systemic anti-tumor treatment for endometrial cancer in the past and are not suitable for radical surgical resection and/or radical concurrent radiotherapy. 5. Agree and can provide sufficient and qualified tumor tissue samples from the primary site or metastatic site (either archived tissue samples from the past 3 years before randomization or fresh tissue samples) for the detection of MMR and PD-L1 status. 6. ECOG PS of 0-1. 7. Adequate organ function. Exclusion Criteria: 1. Second primary malignancy within 5 years before screening. 2. Brain metastases accompanied by central nervous system symptoms. 3. Previously treated with immune checkpoint inhibitors and/or anti-angiogenic drugs. 4. Those who underwent surgery within 4 weeks before the first treatment , or suffered from major traumatic injuries, or were judged by the researchers to have not fully recovered from previous surgeries, or were expected to require surgery during the study period. 5. Arterial hypertension that remains uncontrolled even after receiving standard treatment (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg). 6. Those who have had or currently have interstitial lung disease, pneumoconiosis, drug-related pneumonia, or severely impaired lung function, which may interfere with the detection and management of suspected drug-related pulmonary toxicity. 7. Pregnant or lactating women. 8. Known psychiatric disorder, alcoholism, drug addiction or substance abuse. 9. Participant who, in the opinion of the investigator, are unsuitable to participate in this trial for any other reason.